Substituted ethanolamine esters

ABSTRACT

Compounds of the formula (I): Ar 1  --CH(OH)--CH 2  --NH--CH 2  --X--CH 2  --E--(CH 2 ) n  --Y--Ar 2 , in which the substituents and symbols have the meanings given in the description, are novel active compounds having, in particular, a broncholytic action.

FIELD OF USE OF THE INVENTION

The invention relates to novel compounds, processes for theirpreparation and their use as active compounds in medicaments.

KNOWN TECHNICAL BACKGROUND

German Patent Applications DE 37 04 223 and DE 40 28 398 and EuropeanPatent Applications EP 278 727, EP 278 728, EP 286 242, EP 303 464, EP303 465, EP 303 466 and EP 422 889 describe variously substitutedethanolamine derivatives which, because of their β₂adrenoceptor-agonistic properties, are said to be particularly suitablefor the treatment of diseases of the respiratory passages. BritishPatent 893,088 describes substituted amines which are said to haveantihypertensive and in some cases also spasmolytic properties. Thecompounds disclosed in this patent are phenylethylamines substituted ina particular manner, which are substituted on the nitrogen atom by analkyleneoxycarbonylphenyl radical, where this phenyl radical bondeddirectly to the carbonyl group must be substituted by three hydroxyl oralkoxy groups. German Auslegeschrift 11 26 889 likewise describessubstituted amines (derived from reserpine) having an antihypertensiveand spasmolytic action, in which the phenyl radical bonded directly tothe carbonyl group must be substituted by at least one hydroxyl oralkoxy radical and if appropriate also by a further hydroxyl or alkoxyradical.

DESCRIPTION OF THE INVENTION

A novel group of substituted ethanolamine derivatives which differstructurally from the compounds of the prior art by a hydrolyzable estergroup or by a longer chain length or a quite specific substitution hasnow been found. In a first aspect, the invention thus relates tocompounds of formula I

    Ar.sub.1 --CH(OH)--CH.sub.2 --NH--CH.sub.2 --X--CH.sub.2 --E--(CH.sub.2).sub.n --Y--Ar.sub.2                       (I)

in which

X is 1-12C-alkylene, 1-6C-alkylenoxy-1-6C-alkylene or cyclohexylene,

E is carbonyloxy (--CO--O--) or oxycarbonyl (--O--CO--),

n is an integer from 0 to 10,

Y is a bond, oxygen (O), sulfur (S), the group --CHR--, in which R is1-4C-alkyl, phenyl or hydroxyl, or the group --CR'₂ -- or --CHR'--CH₂O--, in which R' is 1-4C-alkyl, and in which Y is not oxygen if n is thenumber 0,

Ar₁ is a phenyl radical substituted by R1, R2 and R3, in which

R1 is hydrogen, halogen, hydroxyl (--OH), amino (--NH₂), ureido(--NH--CO--NH₂), formylamino (--NH--COH), 1-4C-alkylcarbonylamino(--NH--CO-1-4C-alkyl), di-1-4C-alkyl-carbamoyloxy[--O--CO--N(1-4C-alkyl)₂ ], toluyloxy (--O--CO--C₆ H₄ --CH₃),hydroxymethyl (--CH₂ OH), 1-4C-alkylcarbonyloxy (--O--CO-1-4C-alkyl),1-4C-alkyl, 1-4C-alkoxy, 1-4C-alkylsulfonylamino (--NH--SO₂-1-4C-alkyl), 1-4C-alkylsulfonylmethyl (--CH₂ --SO₂ -1-4C-alkyl) or1-4C-alkoxy-1-4C-alkyl,

R2 is hydrogen, halogen, hydroxyl (--OH), cyano (--CN), trifluoromethyl(--CF₃), toluyloxy (--O--CO--C₆ H₄ --CH₃), hydroxymethyl (--CH₂ OH) or1-4C-alkylcarbonyloxy (--O--CO-1-4C-alkyl) and

R3 is hydrogen or halogen, and

Ar₂ is a phenyl radical which is substituted by R4 and R5, a thienylradical, a pyridyl radical, a naphthyl radical, an indolyl radical, anindanyl radical or a benzo-1,4-dioxanyl radical, in which

R4 is hydrogen, halogen, hydroxyl (--OH), cyano (--CN), 1-4C-alkyl,1-4C-alkoxy, benzyloxy, nitro (--NO₂), trifluoromethyl (--CF₃),1-4C-alkoxycarbonyl (--CO--O-1-4C-alkyl),carbamoyl (--CO--NH₂),di-1-4C-alkylcarbamoyl [--CO--N(1-4C-alkyl)₂ ], amino (--NH₂),1-4C-alkylsulfonyl, phenyl or phenylcarbonylamino and

R5 is hydrogen, halogen, hydroxyl (--OH), 1-4C-alkyl or 1-4C-alkoxy,

and in which R4 is not hydroxyl or 1-4C-alkoxy if E is oxycarbonyl(--O--CO--), n is the number 0 and Y is a bond, and in which R1 and R2are not simultaneously hydroxyl if X is 1-4C-alkylene and E iscarbonyloxy (--CO--O--),

and the salts of these compounds.

1-12C-alkylene is straight-chain or branched alkylene radicals having 1to 12 carbon atoms. Examples which may be mentioned are the radicalsmethylene (--CH₂ --), ethylene (--CH₂ CH₂ --), trimethylene (--CH₂ CH₂CH₂ --), tetramethylene (--CH₂ CH₂ CH₂ CH₂ --), pentamethylene (--CH₂CH₂ CH₂ CH₂ CH₂ --), hexamethylene (--CH₂ --(CH₂)₄ --CH₂ --),octamethylene (--CH₂ --(CH₂)₆ --CH₂ --), decamethylene (--CH₂ --(CH₂)₈--CH₂ --), dodecamethylene (--CH₂ --(CH₂)₁₀ --CH₂ --),1,2-dimethylethylene [--CH(CH₃)--CH(CH₃)--], 1,1-dimethylethylene[--C(CH₃)₂ --CH₂ --], isopropylidene [--C(CH₃)₂ --],2,2-dimethylpropylene [--CH₂ --C(CH₃)₂ --CH₂ --], 2-methylpropylene[--CH₂ --CH(CH₃)--CH₂ --] and 2 -methylethylene [--CH₂ --CH(CH₃)--].

1-6C-alkyleneoxy-1-6C-alkylene is straight-chain or branched alkyleneradicals having 1 to 6 carbon atoms, which are substituted bystraight-chain or branched 1-6C-alkyleneoxy radicals. Examples which maybe mentioned are the ethoxyethylene (--CH₂ --CH₂ --O--CH₂ --CH₂ --) andthe methoxymethylene radical (--CH₂ --O--CH₂ --).

Cyclohexylene radicals which may be mentioned are the 1,2-, the 1,3-and, in particular, the 1,4-cyclohexylene radical.

1-4C-alkyl is straight-chain or branched alkyl radicals having 1 to 4carbon atoms. Examples which may be mentioned are the butyl, isobutyl,sec-butyl, tert-butyl, propyl, isopropyl, ethyl and, in particular, themethyl radical.

Halogen in the context of the present invention is bromine, chlorine andfluorine.

A 1-4C-alkylcarbonylamino radical which may be mentioned is, forexample, the acetylamido radical (--NH--CO--CH₃).

A di-1-4C-alkylcarbamoyloxy radical which may be mentioned is, forexample, the dimethylcarbamoyloxy radical [--O--CO--N(CH₃)₂ ].

1-4C-alkylcarbonyloxy radicals which may be mentioned are, for example,the tert-butylcarbonyloxy radical and the isopropylcarbonyloxy radical.

1-4C-alkoxy radicals contain, in addition to the oxygen atom, one of theabovementioned 1-4C-alkyl radicals. The methoxy radical is preferred.

A 1-4C-alkylsulfonylamino radical which may be mentioned is, forexample, the methylsulfonylamino radical (--NH--SO₂ --CH₃).

A 1-4C-alkylsulfonylmethyl radical which may be mentioned is, forexample, the methylsulfonylmethyl radical (--CH₂ --SO₂ --CH₃).

A 1-4C-alkoxy-1-4C-alkyl radical which may be mentioned is themethoxymethyl radical (--CH₂ --O--CH₃).

Radicals Ar₁ which may be mentioned by way of example are the radicals4-aminophenyl, 3,4-dihydroxyphenyl, 3,5-dihydroxyphenyl,3,5-bis-dimethylaminocarbonyloxyphenyl, 3,5-bis-tolyloxyphenyl,4-hydroxy-3-ureidophenyl, 3-formylamino-4-hydroxyphenyl,4-hydroxyphenyl, 3-amino-5-hydroxyphenyl, 2-fluorophenyl,3-amino-5-hydroxymethylphenyl, 4-amino-3-cyanophenyl,3,5-di-tert-butylcarbonyloxyphenyl, 3,5-diisopropylcarbonyloxyphenyl,2-chloro-4-hydroxyphenyl, 2-fluoro-4-hydroxyphenyl,3-fluoro-4-hydroxyphenyl, 4-hydroxy-3-methoxyphenyl,4-hydroxy-3-methoxymethylphenyl, 4-hydroxy-3-methylsulfonamidophenyl and4-hydroxy-3-methylsulfonylmethylphenyl.

Radicals Ar₁ which may be singled out are the radicals phenyl,2-chlorophenyl, 3-hydroxyphenyl and4-amino-3-chloro-5-trifluoromethylphenyl.

Preferred radicals Ar₁ which may be mentioned are the radicals3-hydroxymethyl-4-hydroxyphenyl, 4-amino-3,5-dichlorophenyl and4-amino-3-chloro-5-cyanophenyl.

1-4C-alkoxycarbonyl radicals R4 which may be mentioned are themethoxycarbonyl and the ethoxycarbonyl radical.

A di-1-4C-alkylcarbamoyl radical R4 which may be mentioned is thediethylcarbamoyl radical.

A 1-4C-alkylsulfonyl radical R4 which may be mentioned is themethylsulfonyl radical.

Radicals Ar₂ which may be singled out are the radicals phenyl,3-fluorophenyl, 4-fluorophenyl, 4-methoxyphenyl,2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 2-nitrophenyl,3-nitrophenyl, 4-nitrophenyl, 2-methylphenyl, 4-methylphenyl,4-benzyloxyphenyl, 3,5-dimethylphenyl, 4-propoxyphenyl, 2-cyanophenyl,4-cyanophenyl, 4-methylsulfonylphenyl, 4-bromophenyl,2-chloro-6-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 4-ethoxyphenyl,2-phenylcarbonylaminophenyl, 2-phenylphenyl, 3-phenylphenyl,4-phenylphenyl, 2-naphthyl, 2-thienyl, 3-thienyl, 3-pyridyl, 2-indanyland 2-benzodioxanyl.

Preferred radicals Ar₂ which may be mentioned are the radicals2-hydroxyphenyl, 3-hydroxyphenyl, 4-hydroxyphenyl, 2-fluorophenyl,3-methylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 2-chlorophenyl,1-naphthyl, 3-indolyl and 2-pyridyl.

Possible salts for compounds of formula I are preferably all the acidaddition salts. The pharmacologically tolerated salts of the inorganicand organic acids usually used in pharmaceuticals may be mentioned inparticular. Pharmacologically non-tolerated salts which, for example,may initially be obtained as process products during preparation of thecompounds according to the invention on an industrial scale areconverted into pharmacologically tolerated salts by processes known tothe expert. Suitable such salts are water-soluble and water-insolubleacid addition salts with acids such as, for example, hydrochloric acid,hydrobromic acid, phosphoric acid, nitric acid, sulfuric acid, aceticacid, citric acid, D-gluconic acid, benzoic acid,2-(4-hydroxybenzoyl)-benzoic acid, butyric acid, sulfosalicylic acid,maleic acid, lauric acid, malic acid, fumaric acid, succinic acid,oxalic acid, tartaric acid, embonic acid, stearic acid, toluenesulfonicacid, methanesulfonic acid or 3-hydroxy-2-naphthoic acid, the acidsbeing employed for the salt preparation in a ratio of amounts which isequimolar or deviates therefrom--depending on whether the acid is mono-or polybasic and depending on what salt is desired.

The compounds of formula I contain at least one chirality center [on thecarbon atom --CH(OH)--], and further chirality centers may alsoadditionally be present by appropriate branchings in the groups X and Y.The invention relates to all the enantiomers and diastereomers as wellas mixtures thereof, including racemates. Compounds of formula I inwhich the substituents on the carbon atom --CH(OH)-- are arranged in theabsolute configuration R (in accordance with rules of Cahn, Ingold andPrelog) are preferred.

Compounds of formula I which are to be singled out are those in which

X is 1-6C-alkylene, 1-2C-alkyleneoxy-1-2C-alkylene or cyclohexylene,

E is carbonyloxy (--CO--O--) or oxycarbonyl (--O--CO--),

n is an integer from 1 to 5,

Y is a bond, oxygen (O) or the group --CHR--, in which R is 1-4C-alkyl,

Ar₁ is a phenyl radical substituted by R1, R2 and R3, in which

R1 is hydrogen, hydroxyl or amino (--NH₂),

R2 is hydrogen, halogen, cyano, trifluoromethyl or hydroxymethyl and

R3 is hydrogen or halogen, and

Ar₂ is a phenyl radical substituted by R4 and R5, a thienyl radical, apyridyl radical, a naphthyl radical, an indolyl radical or an indanylradical, in which

R4 is hydrogen, halogen, hydroxyl (--OH), cyano (--CN), 1-4C-alkyl,1-4C-alkoxy, benzyloxy, nitro (--NO₂) or trifluoromethyl (--CF₃), and

R5 is hydrogen, halogen or 1-4C-alkyl,

and the salts of these compounds.

Compounds of the formula I which are to be singled out in particular arethose in which

X is 3-4C-alkylene,

E is carbonyloxy (--CO--O--) or oxycarbonyl (--O--CO--),

n is the number 1 or 2,

Y is a bond,

Ar₁ is phenyl, 4-amino-3-chloro-5-cyanophenyl,4-hydroxy-3-hydroxymethylphenyl or 4-amino-3,5-dichlorophenyl, and

Ar₂ is a phenyl radical substituted by R4 and R5 or a 1-naphthylradical, in which

R4 is hydrogen, chlorine, fluorine, hydroxyl (--OH), 1-4C-alkyl or1-4C-alkoxy and

R5 is hydrogen,

and the salts of these compounds.

Compounds according to the invention which may be mentioned by way ofexample are

[6-(2-hydroxy-2-phenylethylamino)-1-hexyl]diphenylacetate,

[6-(2-hydroxy-2-phenylethylamino)-1-hexyl]2-phenylbutanoate,

[7-(2-hydroxy-2-phenylethylamino)-1-heptyl]4-phenylbutanoate,

3-phenylpropyl 4-(2-hydroxy-2-phenylethylamino)butanoate,

[6-(2-hydroxy-2-phenylethylamino)-1-hexyl]nicotinate,

2-(2-hydroxyphenoxy)ethyl6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]hexanoate,

{6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}phenylglycolate,

2-(2-trifluoromethylphenyl)ethyl6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]hexanoate,

2-phenylethyl6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]hexanoate,

3-phenylpropyl6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]hexanoate,

5-phenylpentyl6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]hexanoate,

2-(4-benzyloxyphenoxy)ethyl6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]hexanoate,

2-(3,5-dimethylphenoxy)ethyl6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]hexanoate,

3-(4-hydroxyphenyl)propyl6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]hexanoate,

2-(4-propoxyphenoxy)ethyl6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]hexanoate,

4-phenylbutyl [6-(2-hydroxy-2-phenylethylamino)]hexanoate,

2-(2-nitrophenyl)ethyl6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]hexanoate,

2-(2-cyanophenoxy)ethyl6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]hexanoate,

{6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}5-phenylvalerate

and the salts of these compounds.

The invention furthermore relates to a process for the preparation ofcompounds of the formula I and their salts. The process comprises

a) for the preparation of compounds I in which E is oxycarbonyl,reacting compounds of formula II

    Ar.sub.1 --CH(OH)--CH.sub.2 --NH.sub.2                     (II)

in which Ar₁ has the abovementioned meaning, with compounds of formulaIII

    L--CH.sub.2 --X--CH.sub.2 --O--CO--(CH.sub.2).sub.n --Y--Ar.sub.2(III)

in which X, n, Y and Ar₂ have the abovementioned meanings and L is asuitable leaving group, or

b) for the preparation of compounds I in which E is carbonyloxy,reacting compounds of formula II

    Ar.sub.1 --CH(OH)--CH.sub.2 --NH.sub.2                     (II)

in which Ar₁ has the abovementioned meaning, with compounds of formulaIV

    L--CH.sub.2 --X--CH.sub.2 --CO--O--(CH.sub.2).sub.n --Y--Ar.sub.2(IV)

in which X, n, Y and Ar₂ have the abovementioned meanings and L is asuitable leaving group, or

c) for the preparation of compounds I in which E is oxycarbonyl,reacting compounds of formula V

    Ar.sub.1 --CH(OH)--CH.sub.2 --NH--CH.sub.2 --X--CH.sub.2 --OH(V)

in which Ar₁ and X have the abovementioned meanings, with compounds offormula VI

    Z--CO--(CH.sub.2).sub.n --Y--Ar.sub.2                      (VI)

in which n, Y and Ar₂ have the abovementioned meanings and Z is OH(hydroxyl) or a suitable leaving group, and, if desired, subsequentlyconverting compounds I obtained according to a), b) or c) into theirsalts, or, if desired, subsequently liberating the compounds I fromresulting salts of compounds I.

The reaction of compounds II with compounds III and IV is carried out ina manner with which the expert is familiar, in inert, preferably polarsolvents, for example in methanol, ethanol, 1- or 2-propanol,dimethylformamide, tetrahydrofuran, acetone, methyl ethyl ketone, methylisobutyl ketone or dioxane, at temperatures between 10° and 120° C.,preferably between 50° and 100° C. if appropriate at the boiling pointof the solvent used.

The reaction is carried out in the presence of a base, for example atertiary organic amine, such as diisopropylethylamine, or an inorganiccarbonate, such as potassium carbonate.

The expert is familiar with suitable leaving groups L on the basis ofhis expert knowledge. Thus, for example, the tosylate or the mesylategroup, but in particular halogen atoms, and here above all chlorine orbromine, are possible. If chlorine or bromine compounds III or IV areused, the reaction can advantageously also be carried out in thepresence of catalytic amounts of an iodide, such as, for example,potassium iodide.

The reaction of compounds V with compounds VI is carried out in a mannerknown per se, such as is known to the expert on the basis of his expertknowledge of esterification reactions. The esterification is carried outin inert solvents, such as dioxane or tetrahydrofuran, and, depending onthe nature of the group Z, either in the presence of an agent whichsplits off water or bonds water chemically, such as, for example,dicyclohexylcarbodiimide (if Z=OH), or in the presence of4-toluenesulfonic acid, or in the presence of an auxiliary base (forexample triethylamine), if Z is a leaving group, for example a halogenatom (in particular chlorine). The esterification is preferably carriedout starting from the carboxylic acid (Z=OH) in a Dean-Stark apparatusunder acid reaction conditions as described by M. Bodanszky and A.Bodanszky in: "The Practice of Peptide Synthesis" (Springer-Verlag,Berlin, 1984, page 37).

Depending on the nature of the starting compounds, which can also beemployed in the form of their salts, if appropriate, and depending onthe reaction conditions, the compounds according to the invention areinitially obtained either as such or in the form of their salts.

The salts furthermore are obtained by dissolving the free compounds in asuitable solvent, for example in a chlorinated hydrocarbon, such asmethylene chloride or chloroform, a low molecular weight aliphaticalcohol (ethanol or isopropanol), an ether (diisopropyl ether), a ketone(acetone) or water, which contains the desired acid, or to which thedesired acid--if appropriate in the precisely calculated stoichiometricamount--is then added.

The salts are obtained by filtration, reprecipitation, precipitation orby evaporation of the solvent.

Resulting salts can be converted into the free compounds by treatmentwith alkali, for example with aqueous sodium hydrogen carbonate, and thefree compounds can in turn be converted into the salts. The compoundscan be purified in this manner, or pharmacologically non-tolerated saltscan be converted into pharmacologically tolerated salts.

The starting compounds II, III, IV, V and VI are known, or they can beprepared by known processes in an analogous manner, as is described, byway of example, in the examples. Compounds III, for example, can beprepared by reaction of corresponding ω-L-alcohols with suitablecarboxylic acids, and compounds IV can be prepared by reaction ofcorresponding ω-L-carboxylic acids with suitable alcohols (L=leavinggroup, in particular chlorine or bromine). The reaction is in each casecarried out in a Dean-Stark apparatus under acid catalysis, asdescribed, for example, in: Houben-Weyl, Methoden der organischen Chemie[Methods of organic chemistry] VIII/3, pages 503-546. Compounds V areobtained by reaction of correspondingly substituted styrene oxides withsuitable amino alcohols, as described, for example, in: Houben-Weyl,Methoden der organischen Chemie [Methods of organic chemistry] VI/3,pages 366-387.

The following general method descriptions and examples serve toillustrate the invention in more detail. The purity and identity of thecompounds described in the examples have been confirmed using thefollowing methods:

¹ H-nuclear magnetic resonance spectrometry (NMR; Bruker AC 200);

High resolution mass spectrometry (Finnigan MT 90);

Melting point (Mettler FP 5 with microscope) or boiling pointdetermination;

Thin layer chromatography (TLC; E. Merck No. 37333, Kieselgel 60 F₂₅₄)

The invention preferably relates to the compounds of formula I mentionedby name in the examples and the salts of these compounds.

EXAMPLES

Starting compounds

General method description for preparation of compounds III and IV:

A solution of 50 mmol of an alcohol L--CH₂ --X--CH₂ --OH for compoundsIII or of 50 mmol of an alcohol HO--(CH₂)_(n) --Y--Ar₂ (for compoundsIV) is heated with 50 mmol of a carboxylic acid HO--CO--(CH₂)_(n)--Y--Ar₂ (for compounds III) or with 50 mmol of a carboxylic acid L--CH₂--X--CH₂ --CO--OH (for compounds IV) and with 0.5 g of 4-toluenesulfonicacid in toluene in a Dean-Stark apparatus until the reaction has ended(TLC control). The toluene is distilled off and the residue is purifiedby means of distillation, chromatography and/or crystallization. Theidentity of the resulting starting compounds is characterized by meansof ¹ H-NMR.

The following compounds are prepared in accordance with this methoddescription:

A1. 6-bromo-1-hexylbenzoate

From 6-bromo-1-hexanol and benzoic acid. Yield: 85%.

A2. {4-Bromomethyl[trans]cyclohexylmethyl}(3,3-diphenyl)propionate

From 4-bromomethyl[trans]cyclohexylmethanol and 3,3-diphenylpropionicacid. Yield: 60% (oil).

A3. (6-Bromo-1-hexyl)4-phenylbutanoate

From 6-bromo-1-hexanol and 4-phenylbutyric acid. Working up by means ofdistillation. Yield: 72%. Boiling point: 158° C. (0.01 mbar)

A4. (4-Phenylbutyl)6-bromohexanoate

From 6-bromocaproic acid and 4-phenyl-1-butanol. Working up by means ofdistillation. Yield: 80%. Boiling point: 158° C. (0.008 mbar).

A5. (6-Bromo-1-hexyl)3-phenylpropionate

From 6-bromo-1-hexanol and 3-phenylpropionic acid. Yield: 85% (oil).

A6. (12-Bromo-1-dodecyl)4-phenylbutanoate

From 12-bromo-1-dodecanol and 4-phenylbutyric acid. Yield: 85% (oil).

A7. Benzyl 6-bromohexanoate

From benzyl alcohol and 6-bromocaproic acid. Yield: 85% (oil).

A8. (6-Bromo-1-hexyl){3-(4-hydroxyphenyl)}propionate

From 6-bromo-1-hexanol and 3-(4-hydroxyphenyl)propionic acid. Working upby means of distillation. Yield: 70%. Boiling point: 205° C. (0.05mbar).

A9. {4-(Bromomethyl)[trans]cyclohexylmethyl}4-phenylbutanoate

From4-(bromomethyl)[trans]cyclohexylmethanol and 4-phenylbutyric acid.Yield: 80%.

A10. {2-(1-Naphthyl)ethyl}6-bromohexanoate

From 2-(1-naphthyl)ethanol and 6-bromocaproic acid. Working up by meansof distillation. Yield: 88% (oil). Boiling point 150° C. (0.008 mbar).

A11. (3-Phenylpropyl)4-bromobutanoate

From 4-bromobutyric acid and 3-phenylpropanol. Yield: 95%.

A12. (3-Chlorophenyl)3-phenylpropionate

From 3-chloropropanol and 3-phenylpropionic acid. Working up by means ofdistillation. Yield: 88% (oil). Boiling point 115° C. (0.05 mbar).

A13. {2-(3-Thienyl)ethyl}6-bromohexanoate

From 2-(3-thienyl)ethanol and 6-bromocaproic acid. Yield: 70% (oil).

A14. (9-Bromo-1-nonyl)4-phenylbutanoate

From 9-bromo-1-nonanol and 4-phenylbutyric acid. Yield: 78% (oil).

A15. (2-Phenoxyethyl)6-bromohexanoate

From 2-phenoxyethanol and 6-bromocaproic acid. Yield: 80% (oil).

A16. (6-Bromo-1-hexyl)3-fluorophenylacetate

From 6-bromo-1-hexanol and 3-fluorophenylacetic acid. Yield: 70% (oil).

A17. (6-Bromo-1-hexyl)4-(4-methoxyphenyl)butanoate

From 6-bromo-1-hexanol and 4-(4-methoxyphenyl)butyric acid. Yield: 70%(oil).

A18. (6-Chloro-1-hexyl)phenylacetate

From phenylacetic acid and 6-chloro-1-hexanol. Yield: 80%.

A19. Benzyl 6-bromohexanoate

From benzyl alcohol and 6-bromocaproic acid. Yield: 70% (oil).

A20. (6-Bromo-1-hexyl)3-phenylbutanoate

From 3-phenylbutyric acid and 6-bromo-1-hexanol. Yield: 80% (oil).

A21. {2-(4-Methlphenoxy)ethyl}6-bromohexanoate

From 6-bromocaproic acid and 2-(4-methylphenoxy)ethanol. Yield: 80%(oil).

A22. (12-Bromo-1-dodecyl)2-nitrophenylacetate

From 12-bromo-1-dodecanol and 2-nitrophenylacetic acid. Yield: 80%.

A23. {2-(2-Pyridyl)ethyl}6-bromohexanoate

From 6-bromocaproic acid and 2-(2-pyridyl)ethanol. Yield: 70% (oil).

General method description for preparation of the compounds V:

A solution of 0.1 mol of a styrene oxide ##STR1## and 0.1 mol of anamino alcohol NH₂ --CH₂ --X--CH₂ --OH in 250 ml of 2-propanol is heatedat the boiling point under reflux for 8 hours. The solvent is distilledoff and the residue is purified by chromatography.

The following compounds are prepared in accordance with this methoddescription:

B1. 2-(6-Hydroxy-1-hexylamino)1-phenylethanol

From styrene oxide and 6-amino-1-hexanol. Yield after chromatography(methanol): 30% (oil).

B2. 1-(2-Chlorophenyl)2-(6-hydroxy-1-hexylamino)ethanol

From 2-chlorostyrene oxide and 6-amino-1-hexanol. Working up by means ofchromatography (ethyl acetate/methanol 1:1). Yield: 41%.

End products

I. General method description for preparation of the end products fromstarting compounds II and III (process variant a) or from startingcompounds II and IV (process variant b):

A solution of 5 mmol of compound II, 4.5 mmol of compound III or IV, 1.0g of potassium iodide and 3 mmol of diisopropylethylamine in a suitablesolvent is heated (if appropriate at the boiling point under reflux)until the reaction has essentially ended (TLC control). The solvent isdistilled off and the residue is purified by means of chromatographyand/or crystallization. II. General method description for preparationof the end products from the starting compounds V and VI (processvariant c):

A mixture of 5 mmol of the compound V, 5 mmol of compound VI (whereZ=OH), 7 mmol of 4-toluenesulfonic acid and 100 ml of toluene is heatedin a Dean-Stark apparatus for 5 hours. The toluene is evaporated off,the residue is taken up in ethyl acetate and the mixture is extracted byshaking with an aqueous sodium carbonate solution. The organic phase isdried with magnesium sulfate and evaporated. The residue is purified bymeans of chromatography and/or crystallization.

The following compounds are prepared analogously to method description Ior II:

1.{6-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}benzoate-maleate×1/2ethyl acetate

According to method I (tetrahydrofuran, reflux 4 days) from2-amino-1-(4-amino-3,5-dichlorophenyl)ethanol and6-bromo-1-hexylbenzoate. Working up by means of chromatography (ethylacetate/petroleum ether 60-80/triethylamine 6:4:1). Recrystallized asthe maleate from ethyl acetate. Melting point: 78°-79° C.

2. [6-(2-Hydroxy-2-phenylethylamino)-1-hexyl]benzoate-oxalate

According to method II from 2-(6-hydroxy-1-hexylamino)-1-phenylethanoland benzoic acid. Working up by means of chromatography (ethylacetate/methanol 1:1). Recrystallized as the oxalate from acetone.Melting point: 121°-125° C.

3. {6-[2-(2-Chlorophenyl)-2-hydroxyethylamino]-1-hexyl}benzoate-oxalate

According to method II from1-(2-chlorophenyl)-2-(6-hydroxy-1-hexylamino)ethanol and benzoic acid.Working up by means of chromatography (ethyl-acetate/methanol 1:1).Recrystallized as the oxalate from acetone. Melting point: 144°-148° C.

4. {6-[2-(2-Chlorophenyl)-2-hydroxyethylamino]-1-hexyl}-phenylacetate-oxalate

Preparation according to method II from1-(2-chlorophenyl)-2-(6-hydroxy-1-hexylamino)ethanol and phenylaceticacid. Working up by means of chromatography (ethylacetate/methanol/triethylamine 42.5:7.5:1.0). Recrystallized as theoxalate from acetone. Melting point: 114°-117° C.

5. [6-(2-Hydroxy-2-phenylethylamino)-1-hexyl]phenyl acetate-oxalate

According to method II from 2-(6-hydroxy-1-hexylamino)-1-phenylethanoland phenylacetic acid. Working up by means of chromatography (ethylacetate/methanol 1:1). Recrystallized as the oxalate from acetone.Melting point: 116°-121° C.

6.[6-(2-Hydroxy-2-phenylethylamino)-1-hexyl](3,3-diphenyl)propionate-oxalate

According to method II from 2-(6-hydroxy-1-hexylamino)-1-phenylethanoland 3,3-diphenylpropionic acid. Working up by means of chromatography(ethyl acetate/methanol 1:1). Recrystallized as the oxalate fromacetone. Melting point: 136°-139° C.

7.{4-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino-methyl][trans]cyclohexylmethyl}(3,3-diphenylpropionate)maleate

According to method I (tetrahydrofuran, reflux 4 days) from2-amino-1-(4-amino-3,5-dichlorophenyl)ethanol and[4-bromomethyl[trans]cyclohexylmethyl]3,3-diphenylpropionate. Working upby means of chromatography (ethyl acetate/petroleum ether60-80/triethylamine 4:4:1). Recrystallized as the maleate from ethylacetate. Melting point: 156°-158° C.

8.{6-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}4-phenylbutanoate-maleate

According to method I (tetrahydrofuran, reflux 4 days) from2-amino-1-(4-amino-3,5-dichlorophenyl)ethanol and(6-bromo-1-hexyl)4-phenylbutanoate. Working up by means ofchromatography (ethyl acetate/petroleum ether 60-80/triethylamine6:4:1). Recrystallized as the maleate from ethyl acetate. Melting point:69°-74° C.

9. 4-Phenyl-1-butyl6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]hexanoate-maleate

According to method I (tetrahydrofuran, reflux 4 days) from2-amino-1-(4-amino-3,5-dichlorophenyl)ethanol and(4-phenylbutyl)6-bromohexanoate. Working up by means of chromatography(ethyl acetate/petroleum ether 60-80/triethylamine 6:4:1).Recrystallized as the maleate from ethyl acetate. Melting point: 77°-79°C.

10. [6-(2-Hydroxy-2-phenylethylamino)-1-hexyl]5-phenylvalerate-oxalate

According to method II from 2-(6-hydroxy-1-hexylamino)-1-phenylethanoland 5-phenylvaleric acid. Working up by means of chromatography (ethylacetate/methanol 1:1). Recrystallized as the oxalate from acetone.Melting point: 130°-134° C.

11. [6-(2-Hydroxy-2-phenylethylamino)-1-hexyl]4-phenylbutanoate-oxalate

According to method II from 2-(6-hydroxy-1-hexylamino)-1-phenylethanoland 4-phenylbutyric acid. Working up by means of chromatography (ethylacetate/methanol 1:1). Recrystallized as the oxalate from acetone.Melting point: 124°-129° C.

12. [6-(2-Hydroxy-2-phenylethylamino)-1-hexyl]3-phenylpropionate-oxalate

According to method II from 2-(6-hydroxy-1-hexylamino)-1-phenylethanoland 3-phenylpropionic acid. Working up by means of chromatography (ethylacetate/methanol 1:1). Recrystallized as the oxalate from acetone.Melting point: 129°-133° C.

13.4-Phenyl-1-butyl-6-[2-(2-chlorophenyl)-2-hydroxyethylamino]hexanoate-oxalate

According to method I (tetrahydrofuran, reflux 4 days) from2-amino-1-(2-chlorophenyl)ethanol and (4-phenylbutyl)6-bromohexanoate.Working up by means of chromatography (ethyl acetate/petroleum ether60-80/triethylamine 6:4:1). Recrystallized as the oxalate from acetone.Melting point: 149°-150° C.

14.{6-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}3-phenylpropionate-oxalate

According to method I (tetrahydrofuran, reflux 4 days) from2-amino-1-(4-amino-3,5-dichlorophenyl)ethanol and(6-bromo-1-hexyl)3-phenylpropionate. Working up by means ofchromatography (ethyl acetate/petroleum ether 60-80/triethylamine6:4:1). Recrystallized as the oxalate from acetone. Melting point:114°-115° C.

15. [12-(2-Hydroxy-2-phenylethylamino)-1-dodecyl]4-phenylbutanoate

According to method I (tetrahydrofuran, reflux 4 days) from2-amino-1-phenylethanol and (12-bromo-1-dodecyl)4-phenylbutanoate.Working up by means of chromatography (ethyl acetate/petroleum ether60-80/triethylamine 6:4:1). Recrystallized from diethyl ether. Meltingpoint: 73°-74° C.

16. Benzyl[6-(2-hydroxy-2-phenylethylamino)]hexanoate

According to method I (tetrahydrofuran, reflux 4 days) from benzyl6-bromohexanoate and 2-amino-1-phenylethanol. Working up by means ofchromatography (ethyl acetate/methanol/triethylamine 3:1:0.1). Meltingpoint: 77°-78° C.

17.{6-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}[3-(4-hydroxyphenyl)]propionate-hydrochloride

According to method I (dimethylformamide, 2 hours at 90° C.) from2-amino-1-(4-amino-3,5-dichlorophenyl)ethanol and6-bromo-1-hexyl{3-(4-hydroxyphenyl)}propionate. The residue afterevaporation of the solvent is partitioned in ethyl acetate and 0.2Mhydrochloric acid. The organic phase is dried with magnesium sulfate andconcentrated. Melting point: 109°-112° C.

18.{4-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino-methyl][trans]cyclohexylmethyl}4-phenylbutanoate-maleate

According to method I (dimethylformamide, 2 hours at 90° C.) from2-amino-1-(4-amino-3,5-dichlorophenyl)ethanol and{4-(bromomethyl)[trans]cyclohexylmethyl}(4-phenyl)butanoate. Working upby means of chromatography (ethyl acetate/petroleum ether60-80/triethylamine 4:2:1). Recrystallized as the maleate from ethylacetate. Melting point: 155°-157° C.

19. 2-(1-Naphthyl)ethyl6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]hexanoate

According to method I (dimethylformamide, 2 hours at 90° C.) from2-amino-1-(4-amino-3,5-dichlorophenyl)ethanol and{2-(1-naphthyl)ethyl}6-bromohexanoate. Working up by means ofchromatography (ethyl acetate/methanol/triethylamine 16:2:1).Recrystallized as the free base from ethyl acetate. Melting point:60°-61° C.

20.3-Phenylpropyl-4-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]butanoate-maleate

According to method I (dimethylformamide, 2 hours at 90° C.) from2-amino-1-(4-amino-3,5-dichlorophenyl)ethanol and(3-phenylpropyl)-4-bromobutanoate. Working up by means of chromatography(ethyl acetate/methanol/triethylamine 20:2:1). Recrystallized as themaleate from acetone. Melting point: 70°-71° C.

21.{3-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-propyl}3-phenylpropionate-oxalate

According to method I (tetrahydrofuran, reflux 4 days) from2-amino-1-(4-amino-3,5-dichlorophenyl)ethanol and(3-chloropropyl)-3-phenylpropionate. Working up by means ofchromatography (ethyl acetate/triethylamine 8:1). Recrystallized as theoxalate from acetone. Melting point: 133°-134° C.

22.2-(3-Thienyl)ethyl6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]hexanoate

According to method I (tetrahydrofuran, reflux 4 days) from{2-(3-thienyl)ethyl}6-bromohexanoate and2-amino-1-(4-amino-3,5-dichlorophenyl)ethanol. Working up by means ofchromatography (ethyl acetate/triethylamine 8:1). Recrystallized as thebase from diethyl ether. Melting point: 71°-73° C.

23. 9-(2-Hydroxy-2-phenylethylamino)-1-nonyl4-phenylbutanoate-oxalate

According to method I (tetrahydrofuran, reflux 4 days) from(9-bromo-1-nonyl)4-phenylbutanoate and 2-amino-1-phenylethanol. Workingup by means of chromatography (ethyl acetate). Recrystallized as theoxalate from acetone. Melting point: 132°-135° C.

24.2-Phenoxyethyl6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]hexanoate

According to method I (dimethylformamide, 1 hour at 100° C.) from(2-phenoxyethyl)6-bromohexanoate and2-amino-1-(4-amino-3,5-dichlorophenyl)ethanol. Working up by means ofchromatography (ethyl acetate/methanol/triethylamine 16:2:1).Recrystallized as the base from diethyl ether. Melting point: 46°-47° C.

25.{6-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}3-fluorophenylacetate-oxalate

According to method I (dimethylformamide, 3 hours at 90° C.) from(6-bromo-1-hexyl) 3-fluorophenylacetate and2-amino-1-(4-amino-3,5-dichlorophenyl)ethanol. Working up by means ofchromatography (ethyl acetate/methanol/triethylamine 16:2:1).Recrystallized as the oxalate from acetone. Melting point: 70°-71° C.

26.{6-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}4-(4-methoxyphenyl)butanoate-maleate

According to method I (dimethylformamide, 2 hours at 90° C.) from(6-bromo-1-hexyl)4-(4-methoxyphenyl)butanoate and2-amino-1-(4-amino-3,5-dichlorophenyl)ethanol. Working up by means ofchromatography (ethyl acetate/triethylamine 5:1). Recrystallized as themaleate from diethyl ether. Melting point: 66°-67° C.

27.{6-[2-(4-Amino-3.5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}phenylacetate-hemifumarate

According to method I (dimethylformamide, 3 hours at 90° C.) from(6-chloro-1-hexyl)phenylacetate and2-amino-1-(4-amino-3,5-dichlorophenyl)ethanol. Working up by means ofchromatography (ethyl acetate/methanol/triethylamine 8:1:0.5).Recrystallized as the hemifumarate from acetone. Melting point: 79°-82°C.

28.Benzyl6-[2-(4-amino-3,5-dichlorophenyl.)-2-hydroxyethylamino]hexanoate-maleate

According to method I (dimethylformamide, 3 hours at 90° C.) from benzyl6-bromohexanoate and 2-amino-1-(4-amino-3,5-dichlorophenyl)ethanol.Working up by means of chromatography (ethylacetate/methanol/triethylamine 16:2:1). Recrystallized as the maleatefrom diethyl ether. Melting point: 54°-55° C.

29.{6-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}3-phenylbutanoate-maleate

According to method I (dimethylformamide, 3 hours at 90° C.) from(6-bromo-1-hexyl)3-phenylbutanoate and2-amino-1-(4-amino-3,5-dichlorophenyl)ethanol. Working up by means ofchromatography (ethyl acetate/methanol/triethylamine 20:2:1).Recrystallized as the maleate from ethyl acetate. Melting point: 51°-59°C.

30.2-(4-Methylphenoxy)ethyl6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]hexanoate-maleate×1/2ethyl acetate

According to method I (dimethylformamide, 3 hours at 90° C.) from{2-(4-methylphenoxy)ethyl}6-bromohexanoate and2-amino-1-(4-amino-3,5-dichlorophenyl)ethanol. Working up by means ofchromatography (ethyl acetate/methanol/triethylamine 20:2:1).Recrystallized as the maleate from ethyl acetate. Melting point: 77°-78°C.

31.{12-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-dodecyl}2-nitrophenylacetate-oxalate

According to method I (dimethylformamide, 3 hours at 90° C.) from(12-bromo-1-dodecyl)2-nitrophenylacetate and2-amino-1-(4-amino-3,5-dichlorophenyl)ethanol. Working up by means ofchromatography (ethyl acetate/methanol/triethylamine 20:2:1).Recrystallized as the oxalate from acetone. Melting point: 67°-68° C.

32.2-(2-Pyridyl)ethyl6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]hexanoate-hemifumarate

According to method I (dimethylformamide, 1 hour at 90° C.) from{2-(2-pyridyl)ethyl}6-bromohexanoate and2-amino-1-(4-amino-3,5-dichlorophenyl)ethanol. Working up by means ofchromatography (ethyl acetate/methanol/triethylamine 20:2:1).Recrystallized as the hemifumarate from acetone. Melting point: 75°-76°C.

The following compounds are prepared according to method I (indimethylformamide, 3 hours at 100° C.) from corresponding startingcompounds:

33.{6-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}phenoxyacetate,melting point 83°-85° C.

34.{6-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}1-naphthylacetate-maleate,melting point 81°-82° C.

35.{6-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}2-naphthylacetate-hemifumarate,melting point 129°-132° C.

36. 2-(1-Naphthyloxy)ethyl6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]hexanoate, meltingpoint 149°-154° C.

37. 2-(4-Hydroxyphenyl)ethyl6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]hexanoate, meltingpoint 92°-93° C.

38.{6-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}4-methylsulfonyl-3-nitrophenylacetate-hemifumarate,melting point 111°-113° C.

39.{6-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}3-phenoxypropanoate-hemifumarate,melting point 110°-114° C.

40.{4-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-butyl}phenylacetate-hemifumarate,melting point 120°-121° C.

41.{5-[2-(4-Amino-2,3-dichlorophenyl)-2-hydroxyethylamino]-1-pentyl}phenylacetate-hemifumarate,melting point 142°-144° C.

42.{7-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-heptyl}phenylacetate-hemifumarate,melting point 121°-122° C.

43.{8-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-octyl}phenylacetate-hemifumarate,melting point 116°-118° C.

44. 2-Phenylethyl7-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]heptanoate-hemifumarate,melting point 127°-129° C.

45. 2-Phenylethyl8-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]octanoate-hemifumarate,melting point 124°-125° C.

46. 2-Phenylethyl5-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]pentanoate-fumarate,melting point 139°-143° C.

47.{6-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}4-bromophenylacetate-hemifumarate,melting point 129°-130° C.

48. 2,2-Diphenylethyl6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]hexanoate-hemifumarate,melting point 121°-123° C.

49.{6-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}4-phenoxybutanoate-hemifumarate,melting point 112°-113° C.

50. 3-Phenoxy-1-propyl6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]hexanoate-hemifumarate,melting point 105°-107° C.

51.{6-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}2-naphthyloxyacetate-hemifumarate,melting point 113°-116° C.

52.{6-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}2-chloro-6-fluorophenylacetate,melting point 130°-132° C.

53.{8-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-octyl}2-phenoxyacetate-hemifumarate,melting point 124°-125° C.

54. 3-Phenyl-1-propyl5-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]pentanoate-hemifumarate,melting point 107°-111° C.

55. 2-(3-Hydroxyphenyl)ethyl6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]hexanoate-hemifumarate,melting point 157°-159° C.

56. 2-(2-Hydroxyphenyl)ethyl6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]hexanoate-hemifumarate,melting point 97°-98° C.

57. 4-Phenyl-1-butyl5-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]pentanoate-hemifumarate,melting point 130°-132° C.

58. 2-Phenylethyl6-[2-hydroxy-2-(4-hydroxy-3-hydroxymethylphenyl)ethylamino]hexanoate-oxalate,melting point 119°-122° C.

59.{6-[2-Hydroxy-2-(4-hydroxy-3-hydroxymethylphenyl)ethylamino]-1-hexyl}1-naphthylacetate-xinafoate,melting point 125°-128° C.

60.{6-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}2-thienylacetate-hemifumarate,melting point 127°-129° C.

61.{6-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}2-(4-chlorophenyl)-2-methylpropanoate-hemifumarate,melting point 138°-139° C.

62.{6-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}1-naphthyloxyacetate-hemifumarate,melting point 113°-116° C.

63. 2-(3-Hydroxyphenyl)ethyl6-[2-hydroxy-2-(4-hydroxy-3-hydroxymethylphenyl)ethylamino]hexanoate-xinafoate,melting point 67°-69° C.

64. 4-Phenylbutyl6-[2-hydroxy-2-(4-hydroxy-3-hydroxymethylphenyl)ethylamino]hexanoate-oxalate,melting point 119°-121° C.

65. 2-(4-Methylphenyl)ethyl6-[2-(4-amino-2,3-dichlorophenyl)-2-hydroxyethylamino]hexanoate-hemifumarate,melting point 129°-132° C.

66. 2-(4-Fluorophenyl)ethyl6-[2-(4-amino-2,3-dichlorophenyl)-2-hydroxyethylamino]hexanoate-hemifumarate,melting point 138°-141° C.

67.{7-[2-(4-Amino-2,3-dichlorophenyl)-2-hydroxyethylamino]-1-heptyl}benzoate-hemifumarate,melting point 142°-144° C.

68.{5-[2-(4-Amino-2,3-dichlorophenyl)-2-hydroxyethylamino]-1-pentyl}3-phenylpropionate-hemifumarate,melting point 129°-130° C.

69.{6-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}4-nitrophenoxyacetate-hemifumarate,melting point 167°-168° C.

70.{6-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}3-methoxyphenylacetate-hemifumarate,melting point 117°-120° C.

71. 2-Phenylethyl6-[2-(4-amino-3-chloro-5-trifluoromethylphenyl)-2-hydroxyethylamino]hexanoate-hemifumarate,melting point 125°-127° C.

72.{6-[2-(4-Amino-3-chloro-5-trifluoromethylphenyl)-2-hydroxyethylamino]-1-hexyl}1-naphthylacetate-hemifumarate,melting point 141°-144° C.

73. 2-(1-Naphthyl)ethyl6-[2-(4-hydroxy-3-hydroxymethylphenyl)-2-hydroxyethylamino]hexanoate-xinafoate,melting point 151°-153° C.

74. 2-Phenylethyl6-[2-(4-amino-5-chloro-3-cyanophenyl)-2-hydroxyethylamino]hexanoate-hemifumarate,melting point 147°-149° C.

75.{6-[2-Hydroxy-2-(4-hydroxy-3-hydroxymethylphenyl)ethylamino]-1-hexyl}phenylacetate-oxalate,melting point 115°-118° C.

76.{5-[2-Hydroxy-2-(4-hydroxy-3-hydroxymethylphenyl)ethylamino]-1-pentyl}(3-hydroxyphenyl)acetatexinafoate,melting point 95°-100° C.

77.{6-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}4-methoxyphenylacetate-hemifumarate,melting point 119°-120° C.

78.{6-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}2-methoxyphenylacetate-hemifumarate,melting point 123°-124° C.

79{6-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}2-methylphenylacetate,melting point 96°-97° C.

80.{6-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}3-methylphenylacetate-hemifumarate,melting point 130°-132° C.

81.{6-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}2-nitrophenylacetate-hemifumarate,melting point 153°-167° C.

82.{6-[2-(4-Amino-2,3-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}2-chlorophenylacetate-hemifumarate,melting point 138°-141° C.

83.{6-[2-(4-Amino-2,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}3-chlorophenylacetate-hemifumarate,melting point 119°-122° C.

84.{6-[2-(4-Amino-2,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}4-chlorophenylacetate-hemifumarate,melting point 120°-123° C.

85. 1-(2-Phenyl)propyl6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]hexanoate-hemifumarate,melting point 119°-120° C.

86.{5-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-pentyl}3-(1-naphthyl)propionate-hemifumarate,melting point 127°-128° C.

87.{5-[2-Hydroxy-2-(4-hydroxy-3-hydroxymethylphenyl)ethylamino]-1-pentyl}3-(1-naphthyl)propionate-xinafoate,melting point 114°-115° C.

88.{4-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-butyl}4-phenylbutyrate-hemifumarate,melting point 126°-127° C.

89.{6-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}4-cyanophenoxyacetate-hemifumarate,melting point 149°-152° C.

90.{6-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}2-fluorophenylacetate-hemifumarate,melting point 136°-137° C.

91.{6-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}4-ethoxyphenylacetate-hemifumarate,melting point 114°-116° C.

92.{6-[2-(4-Amino-5-chloro-3-cyanophenyl)-2-hydroxyethylamino]-1-hexyl}phenylacetate-hemifumarate,melting point 153° C.

93. 3-(1-Naphthyl)propyl6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]hexanoate-hemifumarate,melting point 153°-155° C.

94. 3-(1-Naphthyl)propyl6-[2-(4-hydroxy-3-hydroxymethylphenyl)-2-hydroxyethylamino]hexanoate-xinafoate,melting point 118°-119° C.

95.{6-[2-(4-Amino-5-chloro-3-cyanophenyl)-2-hydroxyethylamino]-1-hexyl}1-naphthylacetate-hemifumarate,melting point 138°-279° C.

96.{6-[2-Hydroxy-2-(3-hydroxyphenyl)ethylamino]-1-hexyl}1-naphthylacetate-hemifumarate,melting point 117°-131° C.

97.{6-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}11-phenoxyundecanoate,melting point 71°-72° C.

98. 1-Phenoxy-2-propyl6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]hexanoate-hemifumarate,melting point 103°-105° C.

99.{6-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}2-phenylphenoxyacetate-hemifumarate,melting point 116°-118° C.

100.{6-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}3-phenylphenoxyacetate-hemifumarate,melting point<40° C.

101.{6-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}4-phenylphenoxyacetate-hemifumarate,melting point<40° C.

102.{6-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}2-phenytaminocarbonylphenoxyacetate,melting point 105°-107° C.

103. 2-(3-Indolyl)ethyl6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]hexanoate-hemifumarate,melting point 125°-126° C.

104.{6-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}phenylthioacetate-hemifumarate,melting point 154°-155° C.

105. 2-(1,4-Benzodioxanyl)methyl6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]hexanoatehemifumarate,melting point 105°-107° C.

106.{2-[2-[2-(4-Amino-3,5-dichlorophenyl)-2-hydroxyethylamino]ethoxy]ethyl}phenylacetate-fumarate,melting point 118°-120° C.

107. 2-Phenylethyl3-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]propionate-hemifumarate,melting point 128°-131° C.

108. 2-Indanyl6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]hexanoate-fumarate,melting point 123°-129° C.

Commercial usefulness

The compounds according to the invention have valuable pharmacologicalproperties which render them commercially usable. They are primarilyactive β-adrenoceptor agonists (β-sympathomimetics ) havingpreferentially a β₂ -stimulating action, and they are distinguished inparticular by their long duration of action, their stability andselectivity, and by the absence of undesirable side effects.

On the basis of their β-sympathomimetic action, the compounds accordingto the invention are suitable, for example, for treatment ofbradycardias and conduction disturbances and increase the contractilityof the heart, they can be employed as tocolytics for treatment ofpremature labor, they act generally as vasodilators and can be employedfor treatment of (peripheral) circulatory disturbances, they lead to arelaxation of the bladder wall musculature and are suitable fortreatment of disturbed micturition, they lower the (pathologicallyincreased) internal pressure of the eye and can be employed fortreatment of glaucoma, they influence metabolism and are suitable, forexample, for treatment of obesity, and on the basis of their above allβ₂ -sympathomimetic action, they are suitable in particular fortreatment of diseases of the respiratory passages of varying origin.

In particular, bronchial diseases (induced by allergens or inflammation)can be treated on the basis of the broncholytic activity of thecompounds according to the invention. The compounds according to theinvention are distinguished here by a low toxicity, a wide therapeuticrange, a long-lasting action and reduced systemic side effects. In thisconnection, the greatly pronounced activity following topicalapplication--compared with systemic administration--is of particularimportance.

The broncholytic activity of the compounds according to the inventionenables them to be used in human and veterinary medicine, where they areused for treatment and prophylaxis of illnesses based on diseases of thebronchi. For example, acute and chronically obstructive diseases of therespiratory passages of varying origin (bronchitis, allergic bronchitis,bronchial asthma) can be treated in humans and animals. The propertiesof the compounds according to the invention furthermore enable them tobe used for topical treatment of dermatoses, for example forinflammatory and allergic skin diseases, such as toxic and allergiccontact eczema, atopical eczema, seborrheic eczema, follicular andsuperficial pyodermas, endogenous and exogenous acne and acne rosacea.

The compounds according to the invention furthermore are suitable fortreatment of those disease states which are known to be influencedpositively by administration of certain β-adrenoceptor agonists. Thus,for example, on the basis of the hypoglycemic action of the compounds,metabolic disturbances of varying origin (for example obesity ordisturbances such as are related, for example, to diabetes) can betreated. Gastrointestinal motility disturbances and pathological changesin the gastrointestinal tract (for example inflammatory intestinaldiseases, such as Colitis ulcerosa or Crohn's disease) can also betreated by the compounds according to the invention.

The invention therefore also relates to a method for treatment ofmammals, including humans, suffering from one of the abovementioneddiseases. The method comprises administering a therapeutically activeand pharmacologically tolerated amount of one or more of the compoundsaccording to the invention to the sick mammal.

The invention also relates to the compounds according to the inventionfor use for treatment and/or prophylaxis of the diseases mentioned.

The invention furthermore relates to the use of the compounds accordingto the invention for the preparation of medicaments which are employedfor treatment and/or prophylaxis of the diseases mentioned.

The invention furthermore relates to medicaments for treatment and/orprophylaxis of the diseases mentioned which comprise one or more of thecompounds according to the invention and/or their pharmacologicallytolerated salts.

The medicaments according to the invention are prepared by processesknown per se, reference being made to, for example, the statements inEuropean Patent 163 965 in respect of the formulations, the dosage forms(especially in respect of administration by inhalation) and the like. Inthis connection, administration by inhalation, for which the compoundsaccording to the invention seem outstandingly suitable on the basis oftheir action profile, is of particular importance in the treatment ofbronchial diseases.

If the compounds according to the invention are to be administered byinhalation, daily doses of 0.01 to 2.0 mg, in particular 0.05 to 1.0 mg,advantageously in several individual doses of, for example, 10 to 50 μgof active compound, are administered. For oral administration,correspondingly higher dosages (from 0.5 to 50 mg per day), ifappropriate in the form of several individual doses, are to beadministered.

Pharmacology

The excellent bronchospasmolytic action of the compounds according tothe invention can be demonstrated by in vitro studies on the guinea pigtrachea. For this, the relaxing action on a guinea pig trachea which hasbeen contracted beforehand with a suitable dose of methacholine ismeasured for the compounds to be investigated. The trachea of maleguinea pigs (200-300 g) is removed and divided into individual segmentsand each segment is suspended in an organ bath with 118.5 mM NaCl, 4.7mM KCl, 1.2 mM MgSO₄, 2.5 mM CaCl₂, 1.2 mM KH₂ PO₄, 25 mM NaHCO₃ and 10mM glucose at 37° C. Oxygen to which 5% of CO₂ has been added is passedpermanently through the solution. After stabilization, the trachea iscontracted with a suitable dose of methacholine. Thereafter, adose/effect curve is plotted with the test substances in a cumulativemanner. The concentration (mol/l) which corresponds to 50% of themaximum effect (EC₅₀) is then determined from this curve. This EC₅₀ isthus a measure of the activity of the compounds according to theinvention.

The -log[EC₅₀ (mol/l)] value for selected compounds according to theinvention are shown in the following table. The serial number in thetable agrees with the number of the compounds in the examples. Thenumber n indicates the number of investigations.

                  TABLE                                                           ______________________________________                                        Serial No.      -log[EC.sub.50 ]                                                                         n                                                  ______________________________________                                        17              7.7        6                                                  19              8.2        3                                                  32              7.8        3                                                  34              8.5        5                                                  37              8.7        6                                                  64              8.0        4                                                  74              8.4        6                                                  82              8.0        6                                                  103             8.5        5                                                  106             8.1        3                                                  ______________________________________                                    

We claim:
 1. A compound of formula I

    Ar.sub.1 --CH(OH)--CH.sub.2 --NH--CH.sub.2 --X--CH.sub.2 --E--(CH.sub.2).sub.n --Y--Ar.sub.2                       (I)

in which X is 1-12C-alkylene, 1-6C-alkyleneoxy-1-6C-alkylene orcyclohexylene, E is carbonyloxy (--CO--O--) or oxycarbonyl (--O--CO--),n is an integer from 0 to 10, Y is a bond, oxygen (O), sulfur (S), thegroup --CHR--, in which R is 1-4C-alkyl, phenyl or hydroxyl, or thegroup --CR'₂ -- or --CHR'--CH₂ O--, in which R' is 1-4C-alkyl, and inwhich Y is not oxygen if n is the number 0, Ar₁ is a phenyl radicalsubstituted by R1, R2 and R3, in whichR1 is hydrogen, halogen, hydroxyl(--OH), amino (--NH₂), ureido (--NH--CO--NH₂), formylamino (--NH--COH),1-4C-alkylcarbonylamino (--NH--CO-1-4C-alkyl),di-1-4C-alkyl-carbamoyloxy [--O--CO--N(1-4C-alkyl)₂ ], toluyloxy(--O--CO--C₆ H₄ --CH₃), hydroxymethyl (--CH₂ OH), 1-4C-alkylcarbonyloxy(--O--CO-1-4C-alkyl), 1-4C-alkyl, 1-4C-alkoxy, 1-4C-alkylsulfonylamino(--NH--SO₂ -1-4C-alkyl), 1-4C-alkylsulfonylmethyl (--CH₂ --SO₂-1-4C-alkyl) or 1-4C-alkoxy-1-4C-alkyl, R2 is hydrogen, halogen,hydroxyl (--OH), cyano (--CN), trifluoromethyl (--CF₃), toluyloxy(--O--CO--C₆ H₄ --CH₃), hydroxymethyl (--CH₂ OH) or1-4C-alkylcarbonyloxy (--O--CO-1-4C-alkyl) and R3 is hydrogen orhalogen, and Ar₂ is a phenyl radical which is substituted by R4 and R5,a thienyl radical, a pyridyl radical, a naphthyl radical, an indolylradical, an indanyl radical or a benzo-1,4-dioxanyl radical, in whichR4is hydrogen, halogen, hydroxyl (--OH), cyano (--CN), 1-4C-alkyl,1-4C-alkoxy, benzyloxy, nitro (--NO₂), trifluoromethyl (--CF₃),1-4C-alkoxycarbonyl (--CO--O-1-4C-alkyl), carbamoyl (--CO--NH₂),di-1-4C-alkylcarbamoyl [--CON--(1-4C-alkyl)₂ ], amino (--NH₂),1-4C-alkylsulfonyl, phenyl or phenylcarbonylamino and R5 is hydrogen,halogen, hydroxyl (--OH), 1-4C-alkyl or 1-4C-alkoxy, and in which R4 isnot hydroxyl or 1-4C-alkoxy if E is oxycarbonyl (--O--CO--), n is thenumber 0 and Y is a bond, and in which R1 and R2 are not simultaneouslyhydroxyl if X is 1-4C-alkylene and E is carbonyloxy (--CO--O--), or asalt of this compound.
 2. A compound of formula I as claimed in claim 1,in whichX is 1-12C-alkylene or cyclohexylene, E is carbonyloxy(--CO--O--) or oxycarbonyl (--O--CO--), n is an integer from 0 to 8, Yis a bond, oxygen (O) or the group --CHR--, in which R is 1-4C-alkyl,phenyl or hydroxyl, and in which Y is not oxygen if n is the number 0,Ar₁ is a phenyl radical substituted by R1, R2 and R3, in whichR1 ishydrogen, halogen, hydroxyl (--OH), amino (--NH₂), ureido(--NH--CO--NH₂), formylamino (--NH--COH), 1-4C-alkylcarbonylamino(--NH--CO-1-4C-alkyl), di-1-4C-alkyl-carbamoyloxy[--O--CO--N(1-4C-alkyl)₂ ], toluyloxy (--O--CO--C₆ H₄ --CH₃),hydroxymethyl (--CH₂ OH), 1-4C-alkylcarbonyloxy (--O--CO-1-4C-alkyl),1-4C-alkyl, 1-4C-alkoxy, 1-4C-alkylsulfonylamino (--NH--SO₂-1-4C-alkyl), 1-4C-alkylsulfonylmethyl (--CH₂ --SO₂ -1-4C-alkyl) or1-4C-alkoxy-1-4C-alkyl, R2 is hydrogen, halogen, hydroxyl (--OH), cyano(--CN), trifluoromethyl (--CF₃), toluyloxy (--O--CO--C₆ H₄ --CH₃),hydroxymethyl (--CH₂ OH) or 1-4C-alkylcarbonyloxy (--O--CO-1-4C-alkyl)and R3 is hydrogen or halogen, and Ar₂ is a phenyl radical substitutedby R4 and R5, a thienyl radical, a pyridyl radical or a naphthylradical, in whichR4 is hydrogen, halogen, hydroxyl (--OH), cyano (--CN),1-4C-alkyl, 1-4C-alkoxy, benzyloxy, nitro (--NO₂), trifluoromethyl(--CF₃), 1-4C-alkoxycarbonyl (--CO--O-1-4C-alkyl), carbamoyl(--CO--NH₂), di-1-4C-alkylcarbamoyl [--CO--N(1-4C-alkyl)₂ ] or amino(--NH₂) and R5 is hydrogen, halogen, hydroxyl (--OH), 1-4C-alkyl or1-4C-alkoxy, and in which R4 is not hydroxyl or 1-4C-alkoxy if E isoxycarbonyl (--O--CO--), n is the number 0 and Y is a bond, and in whichR1 and R2 are not simultaneously hydroxyl if X is 1-4C-alkylene and E iscarbonyloxy (--CO--O--), or a salt of this compound.
 3. A compound offormula I as claimed in claim 1, in which n is an integer from 1 to 10,or a salt of this compound.
 4. A compound of formula I as claimed inclaim 1, in which E is carbonyloxy (--CO--O--), or a salt of thiscompound.
 5. A compound of formula I as claimed in claim 1, in which Eis oxycarbonyl (--O--CO--), or a salt of this compound.
 6. A compound offormula I as claimed in claim 1, in whichX is 1-6C-alkylene,1-2C-alkyleneoxy-1-2C-alkylene or cyclohexylene, E is carbonyloxy(--CO--O--) or oxycarbonyl (--O--CO--), n is an integer from 1 to 5, Yis a bond, oxygen (O) or the group --CHR--, in which R is 1-4C-alkyl,Ar₁ is a phenyl radical substituted by R1, R2 and R3, in whichR1 ishydrogen, hydroxyl or amino (--NH₂), R2 is hydrogen, halogen, cyano,trifluoromethyl or hydroxymethyl and R3 is hydrogen or halogen, and Ar₂is a phenyl radical substituted by R4 and R5, a thienyl radical, apyridyl radical, a naphthyl radical, an indolyl radical or an indanylradical, in whichR4 is hydrogen, halogen, hydroxyl (--OH), cyano (--CN),1-4C-alkyl, 1-4C-alkoxy, benzyloxy, nitro (--NO₂) or trifluoromethyl(--CF₃), and R5 is hydrogen, halogen or 1-4C-alkyl, or a salt of thiscompound.
 7. A compound of formula I as claimed in claim 1, in whichX is3-4C-alkylene, E is carbonyloxy (--CO--O--) or oxycarbonyl (--O--CO--),n is the number 1 or 2, Y is a bond, Ar₁ is phenyl,4-amino-3-chloro-5-cyanophenyl, 4-amino-hydroxy-3-hydroxymethylphenyl or4-amino-3,5-dichlorophenyl, and Ar₂ is a phenyl radical substituted byR4 and R5 or a 1-naphthyl radical, in whichR4 is hydrogen, chlorine,fluorine, hydroxyl (--OH), 1-4C-alkyl or 1-4C-alkoxy and R5 is hydrogen,or a salt of this compound.
 8. A compound of formula I as claimed inclaim 1, in whichX is 1-6C-alkylene, E is carbonyloxy (--CO--O--) oroxycarbonyl (--O--CO--), n is an integer from 1 to 3, Y is a bond,oxygen (O) or the group --CHR--, in which R is 1-4C-alkyl, Ar₁ is phenylor 4-amino-3,5-dichlorophenyl, and Ar₂ is a phenyl radical substitutedby R4 and R5, a 3-thienyl radical, a 2-pyridyl radical or a 1-naphthylradical, in whichR4 is hydrogen, fluorine, hydroxyl (--OH), 1-4C-alkylor 1-4C-alkoxy and R5 is hydrogen or 1-4C-alkyl, or a salt of thiscompound.
 9. A compound as claimed in claim 1, selected from the groupconsisting of2-(1-naphthyl)ethyl6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]hexanoate,{6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}1-naphthylacetate,2-(4-hydroxyphenyl)ethyl6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]hexanoate,{5-[2-(4-amino-2,3-dichlorophenyl)-2-hydroxyethylamino]-1-pentyl}phenylacetate,2-(3-hydroxyphenyl)ethyl6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]hexanoate,2-(2-hydroxyphenyl)ethyl6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]hexanoate,2-phenylethyl6-[2-hydroxy-2-(4-hydroxy-3-hydroxymethylphenyl)ethylamino]hexanoate,{6-[2-hydroxy-2-(4-hydroxy-3-hydroxymethylphenyl)ethylamino]-1-hexyl}1-naphthylacetate,2-(3-hydroxyphenyl)ethyl6-[2-hydroxy-2-(4-hydroxy-3-hydroxymethylphenyl)ethylamino]hexanoate,4-phenylbutyl6-[2-hydroxy-2-(4-hydroxy-3-hydroxymethylphenyl)ethylamino]hexanoate,{6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}3-methoxyphenylacetate,2-(1-naphthyl)ethyl6-[2-(4-hydroxy-3-hydroxymethylphenyl)-2-hydroxyethylamino]hexanoate,2-phenylethyl6-[2-(4-amino-5-chloro-3-cyanophenyl)-2-hydroxyethylamino]hexanoate,{6-[2-hydroxy-2-(4-hydroxy-3-hydroxymethylphenyl)ethylamino]-1-hexyl}phenylacetate,{5-[2-hydroxy-2-(4-hydroxy-3-hydroxymethylphenyl)ethylamino]-1-pentyl}(3-hydroxyphenyl)acetate,{6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}2-methoxyphenylacetate,{6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}3-methylphenylacetate,{6-[2-(4-amino-2,3-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}2-chlorophenylacetate,{5-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-pentyl}3-(1-naphthyl)propionate,{5-[2-hydroxy-2-(4-hydroxy-3-hydroxymethylphenyl)ethylamino]-1-pentyl}3-(1-naphthyl)propionate,{6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]-1-hexyl}2-fluorophenylacetate,2-(3-indolyl)ethyl6-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]hexanoate and{2-[2-[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethylamino]ethoxy]ethyl}phenylacetateor a salt thereof.
 10. A medicament composition comprising a suitablecarrier and an effect amount of a compound of formula I as claimed inclaim 1 or a pharmacologically-tolerated salt thereof.
 11. In a methodof treating a disease of the bronchi by administering an effectiveamount of active ingredient to a human or other animal afflicted withsuch disease, the improvement wherein the active ingredient is acompound of claim 1 or a pharmacologically-tolerated salt thereof.